Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches
Abstract
The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster the efficacy of azole-based treatments. Drug repurposing stands as a promising and practical avenue for advancing antifungal therapy, with the potential for swift clinical translation. This review offers a comprehensive overview of azole synergistic agents uncovered through drug repurposing strategies, alongside an in-depth exploration of the mechanisms by which these agents augment azole potency. Drawing from these mechanisms, we delineate strategies aimed at enhancing azole effectiveness, such as inhibiting efflux pumps to elevate azole concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating fungal cell resistance to azoles, and disrupting biological processes extending beyond ergosterol synthesis. This review is beneficial for the development of these potentiators, as it meticulously examines instances and provides nuanced discussions on the mechanisms underlying the progression of azole potentiators through drug repurposing strategies.
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Self-citationSynthesis and Antifungal Evaluation Against Candida spp. of 5-Arylfuran-2-Carboxamide Derivatives
Mirabile, S., Ginestra, G., Pennisi, R., Barreca, D., Mandalari, G., & Gitto, R. (2025) · Microorganisms · doi:10.3390/microorganisms13081835
Feng, Y., Zhen, C., Li, W., Whiteway, M. S., Fang, X., Shen, X., Jiang, Y., & Lu, H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.15.676225
Self-citationPrabakaran, A., & Sinha, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.22.701080
Neto, J. X. D. S., da Silva, A. P. A., Guedes, M. I. F., & Sousa, D. O. B. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.151760
Silvaraju, G., Borzehandani, M. Y., Johari, N. A. S., Saad, N., Razali, R., Shaarani, S. H. N., & Kamal, N. A. M. A. (2026) · ACS Applied Bio Materials · doi:10.1021/acsabm.6c00092
Feng, Y., Zhen, C., Li, W., Whiteway, M. S., Fang, X., Shen, X., Jiang, Y., & Lu, H. (2026) · Microbiological Research · doi:10.1016/j.micres.2026.128595 · Cited by 2 · see citing works
Self-citationImtiaz, M. S., Persoons, L., Daelemans, D., Jonghe, S. D., & Hameed, S. (2026) · RSC Advances · doi:10.1039/d6ra03835b
Hang, S., Jiang, B., Li, W., Xu, X., Xu, L., Xiong, J., Jiang, Y., & Lu, H. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118302 · Cited by 1 · see citing works
Self-citation
- Authors
- Xiong, J., Lu, H., & Jiang, Y.
- Affiliations
- Tongji University (CN)
- Corresponding author
- Lu, Hui
- Jiang, Yuanying
- Venue
- ACS Infectious Diseases
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-01-03
- Volume
- 11
- Issue
- 2
- Pages
- 305-322
- ISSN
- 2373-8227 (ISSN-L)
- OpenAlex
- W4406035076
- Cited by
- 20
- References
- 188
- Citations by year
- 2026: 11 · 2025: 9
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shanghai Municipal Education Commission (202101070007-E00094)
- National Natural Science Foundation of China (82020108032)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- drug repurposing, azole resistance, fungal pathogens, antifungal therapy, efflux pump inhibition, ergosterol synthesis inhibition, fungal cell wall
- MeSH terms
- Antifungal Agents, Azoles, Drug Synergism, Fungi, Humans, Microbial Sensitivity Tests, Mycoses, Drug Resistance, Fungal, Drug Repositioning
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